26 - World Journal of Gastroenterology

esponse of the tumor was seen in only 10% of the patients,
and the 1-, 2-, and 3-year survival rates were 68%,
37% and 0%, respectively with TACE alone, and histologic
examinations showed that TACE alone caused complete
necrosis in only 20% of the tumors. In contrast, PEA
combined with TACE significantly increased the partial
response rate (45%), prolonged the 1-, 2-, and 3-year survival
rates (100%, 85% and 85%), and achieved complete
histologic necrosis in 83% of the tumors. Dohmen et al [15]
proved that the combined TACE and PEA treatment had
a lower incidence of local recurrence than TACE alone
which resulted in an increased survival of the patients with
unresectable large HCC.
Ethanol in PEA diffused within the cells, causing immediate
dehydration of cytoplasmic proteins with consequent
coagulation necrosis followed by fibrosis, and entered the
circulation, inducing necrosis of endothelial cells and platelet
aggregation with consequent thrombosis of small vessels
followed by ischemia of the neoplastic tissues. Advantages
of PEA were [16-18] : no remarkable damage to the remaining
parenchyma, being safe, easy to be repeated when new
lesions appear, low in cost, easy to operate, and possessing
good long-term results. PEA can be carried out either in patients
with HCC who have a poor liver function or in elderly
patients (age ≥ 70 years) [19,20] . Our results proved that higher
doses of ethanol can be injected, which can achieve complete
and homogeneous perfusion even in large lesions.
It is necessary to analyze prognostic factors in a large
number of patients in sufficient detail and to evaluate the
result of each method of treatment between groups with
similar prognostic factors. Our study showed that only the
number of tumors, tumor margin and the total ethanol
dose were independent factors predicting survival. Although
various prognostic factors have been reported [21-23] ,
no conclusion has been drawn as to which factor is significant.
In this study, the significant factors for better prognosis
included the number of tumors, tumor margin and
the total ethanol dose. The prognostic factors identified
in this study suggested that, therapeutic results in patients
with solitary tumors and clear tumor margin treated at a
higher total ethanol dose should be better than those in
patients with multiple tumors, without clear tumor margin
treated at a lower total ethanol dose. It is worth noting the
tumor margin is one of the important prognostic factors.
It is determined based on hepatobiliary phase images and
represents the growth pattern of tumor to some extent.
The tumor margin imaging can predict microscopic portal
vein invasion, intrahepatic metastasis and early recurrence
after hepatectomy in HCC patients [24] .
Ebara et al [25] and Vilana et al [26] proposed tumors <
30 mm in size and < 3 in number as indications for PEA,
mainly because of technical limitation such as the inability
to inject an effective volume of ethanol into the whole
area of the tumor. Our results suggested that some tumors
> 50 mm in size could be treated by PEA because
the therapeutic results of PEA were also good for large
HCC patients with solitary tumors and clear tumor margin
at a higher total ethanol dose after TACE.
WJG|www.wjgnet.com
Gao F et al . Combined therapy for large hepatocellular carcinoma
Long-term survival rates of PEA-treated patients are
similar to those obtained in matched patients undergoing
partial hepatectomy [27,28] . However, the long-term prognosis
remains disappointing because of the high recurrence
rate among patients with HCC after PEA, especially in
those with multiple lesions, cirrhosis and a high level of
AFP and those without a clear tumor margin and peritumoral
capsule [29,30] . In fact, histological examination of
HCC after PEA reveals that residual tumor tissues remain
in portions isolated by septa or with extracapsular or intracapsular
invasion. It has been demonstrated that the
high vascularity of HCC promotes an early wash-out of
injected ethanol, so that PEA for patients with hypervascular
tumors may be less effective than for patients with
hypovascular tumors [31,32] .
COMMENTS
Background
The incidence of large hepatocellular carcinoma (HCC) is increasing in China
and HCC has a poor prognosis due to its rapid infiltration and complicating liver
cirrhosis. The results in this study indicated that combined transcatheter arterial
chemoembolization (TACE) with percutaneous ethanol ablation (PEA) is a
promising therapeutic approach for large unresectable HCC.
Research frontiers
The authors analyzed the prognostic factors in a large number of patients in detail
and evaluated the result of each method of treatment between groups with
similar prognostic factors. This study showed that the number of tumors, tumor
margin and the total ethanol dose were independent factors predicting survival.
Innovations and breakthroughs
This is the first study to report that the number of tumors, tumor margin and the
total ethanol dose were independent factors predicting survival of large HCC.
The combined TACE and PEA therapy is a promising approach for large unresectable
HCC.
Applications
By understanding the independent prognostic factors, this study may represent
a future strategy in the treatment of patients with large unresectable HCC.
Terminology
TACE has become one of the most popular approaches of non-surgical treatment,
with good results in reducing the tumor size of HCC and improving the
survival of the patients. PEA is facilitated by the TACE-derived fibrous wall
around the lesion, which favors a better retention of the injected ethanol within
the tumor.
Peer review
This is a constructive study to report that the number of tumors, tumor margin
and the total ethanol dose were independent factors predicting survival of large
HCC, which is expected to improve the therapeutic effects for large unresectable
HCC.
REFERENCES
1 Yamada R, Kishi K, Sato M, Sonomura T, Nishida N,
Tanaka K, Shioyama Y, Terada M, Kimura M. Transcatheter
arterial chemoembolization (TACE) in the treatment of unresectable
liver cancer. World J Surg 1995; 19: 795-800
2 Mondazzi L, Bottelli R, Brambilla G, Rampoldi A, Rezakovic
I, Zavaglia C, Alberti A, Ideo G. Transarterial oily chemoembolization
for the treatment of hepatocellular carcinoma:
a multivariate analysis of prognostic factors. Hepatology
1994; 19: 1115-1123
3 Hatanaka Y, Yamashita Y, Takahashi M, Koga Y, Saito R,
Nakashima K, Urata J, Miyao M. Unresectable hepatocellular
carcinoma: analysis of prognostic factors in transcatheter
management. Radiology 1995; 195: 747-752
3149 July 14, 2011|Volume 17|Issue 26|